Asymmetric reaction for drug synthesis

15 Dec 2014 NUS scientist was selected as one of the finalists in Singapore for the MIT TR for innovators under age 35.

The Judges and Steering Committee of MIT Technology Review’s EmTech Singapore have named Prof YEUNG Ying Yeung from the Department of Chemistry in NUS as one of the top 10 finalists of the regional MIT TR35 Innovators Under 35 APAC competition due to his breakthrough innovation in the development of asymmetric halogenation. He will make a brief presentation about his work in the MIT Technology Review’s EmTech Singapore conference on 27-28 Jan 2015.

The ability to design elegant and economical synthesis routes is a major factor in the eventual viability and commercial success of a drug. In modern drug synthesis, an equally important target is to make only one hand of the mirror-image pair of molecules through asymmetric synthesis since in many cases one hand can be life-saving and the opposite hand can be fatal.

Halogenation reaction, a well-developed and key organic transformation, plays a crucial role in pharmaceutical industry. However, the asymmetric variant of halogenation remains uncommon due to some inherent difficulties and it challenged chemists over the past 50 years.

Nonetheless, Prof YEUNG Ying Yeung and his team envisioned that the successful development of novel the bromination (an important class of halogenation) reaction would allow us to obtain a powerful tool in the synthesis of various heterocyclic compounds. Recently, Yeung’s team devised a sulfide base-catalyzed enantioselective bromination protocol. A unique sulfide basic catalyst is used in the enantioselective bromination to mediate the asymmetric delivery of a bromine atom. The reaction can be applied in the synthesis of a range of chiral bromolactones, bromoethers, bromopyrrolidines, and bromopiperidines. These molecules are valuable building blocks for drug synthesis (see Figure).

More details on the application can be found here. http://www.emtechsingapore.com/index.php/innovators-under-35

YeungYY

The figure shows the sulfide base catalyzed asymmetric bromination in the synthesis of an advanced intermediate of the antifungal drug Posaconazole. [Image credit: YEUNG Ying Yeung]

 

Reference

Ke Z, Tan CK, Yeung YY. “Catalytic Asymmetric Bromoetherification and Desymmetrization of Olefinic 1,3-Diol with C2-Symmetric Sulfides.” Journal of the American Chemical Society. 136 (2014) 5627.